Journal Article

DKFZ-2026-02600

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dissecting the functional and spatial roles of peroxiredoxins as H2O2 scavengers and redox transducers.

de Cubas, L. (First author)DKFZ* ; Konopko, A. ; Boronat, S. ; Ayté, J. ; Hidalgo, E.

2026
Springer International Publishing AG Cham (ZG)

Abstract: Since their discovery in the late 1980s as peroxidases that eliminate hydrogen peroxide (H2O2), peroxiredoxins (Prxs) have been recognized not only for detoxification but also for roles in redox signaling. In fission yeast, the main Prx, Tpx1, maintains steady-state H2O2 below toxic levels through its scavenging activity. Under excess peroxides, Tpx1 switches to a signaling role, transmitting oxidative signals to the transcription factor Pap1. Dissecting the relative contributions of Tpx1's peroxidase and sensor functions is challenging. To address this, we used a synthetic biology strategy to separate these dual roles. Tpx1 or catalase (Ctt1) was expressed in distinct subcellular compartments, and their capacity to remove H2O2 and activate Pap1 was assessed. Both scavengers can complement the growth defects of cells lacking Tpx1 in high oxygen. Combined with H2O2 biosensors, our results show that Tpx1 efficiently controls H2O2 levels from any compartment, whereas Ctt1 does not. However, cells expressing mitochondrial- or nuclear-targeted Tpx1 display reduced oxidative stress tolerance because Pap1 activation requires cytosolic Tpx1. Overall, Tpx1 is a highly effective peroxidase throughout the cell, but its subcellular localization is essential for proper redox signaling regulation.

Keyword(s): Hydrogen Peroxide: metabolism (MeSH) ; Peroxiredoxins: metabolism (MeSH) ; Peroxiredoxins: genetics (MeSH) ; Schizosaccharomyces pombe Proteins: metabolism (MeSH) ; Schizosaccharomyces pombe Proteins: genetics (MeSH) ; Schizosaccharomyces: metabolism (MeSH) ; Schizosaccharomyces: genetics (MeSH) ; Oxidation-Reduction (MeSH) ; Pancreatitis-Associated Proteins (MeSH) ; Signal Transduction (MeSH) ; Basic-Leucine Zipper Transcription Factors: metabolism (MeSH) ; Basic-Leucine Zipper Transcription Factors: genetics (MeSH) ; Catalase: metabolism (MeSH) ; Catalase: genetics (MeSH) ; Genetically encoded fluorescent H2O2 reporter ; H2O2 levels ; H2O2 sensor ; HyPer7 ; Prx ; Hydrogen Peroxide ; Peroxiredoxins ; Schizosaccharomyces pombe Proteins ; Pap1 protein, S pombe ; Pancreatitis-Associated Proteins ; Tpx1 protein, S pombe ; Basic-Leucine Zipper Transcription Factors ; Catalase

Note: #EA:A160# / DKFZ-ZMBH Alliance

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Contributing Institute(s):

1. Redoxregulation (A160)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2026

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